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目的：探讨Notch 信号特异性阻断剂γ- 分泌酶抑制剂（DAPT）对AGEs 作用下的心肌微血管内皮细胞的增殖、迁移、管样结构的影响。方法：SD 大鼠心肌微血管内皮细胞体外分离培养后，以不同浓度DAPT（0.25、0.5、1.0、5.0、10 μmol/L）干预200mg/L AGEs 作用下的CMECs24h，或者与DAPT（5 μmol/L）孵育不同时间（24h、48h、72h、96h、120h），采用MTT 比色法检测细胞的增值能力；用Transwell 法检测细胞的迁移能力；用毛细血管管样结构形成实验检测DAPT 对血管新生的影响。结果：DAPT 显著抑制 AGEs 作用下的心肌微血管内皮细胞的存活，同时浓度越高、时间越长，其抑制效果越明显。结论：DAPT 通过阻断Notch 信号通路，能抑制AGEs 作用下的心肌微血管内皮细胞的增殖及血管新生，促进细胞凋亡。

英文摘要:

Objective：To investigate the effect of DAPT under the advanced glycation end products (AGEs) on proliferation, migration, angiogenesis and lumen formation of cardiac microvascular endothelial cells (CMECs). Methods: CMECs isolated from the hearts of adult rats were exposed to hypoxia (94%N2, 5%CO2, 1%O2). The cells were incubated with different concentrations (in μmol/L: 0,0.25,0.5,1.0,5.0,10.0) of DAPT for 24h, or incubated with DAPT (5 μmol/L) for 24h,48h, 72h,96h and 120h.The cell viability of CMECs was measured by MTT method and migration ability of CMECs was detected by Tranwell method. Capillary lumen formation test was applied to detect the angiogenesis. Results: The viability of CMECs depressed with DAPT incubation. Conclusion: DAPT can interrupt the transduction of Notch signaling pathway in cardiac microvascular endothelial cells (CMECs) and inhibit the viability of the cells and increase their apoptosis.

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